Sudden or rapidly progressive sensorineural hearing loss and/or specific balance disorders appear to be related to perilymphatic fistulas (PLF). This statement is based on both clinical and human temporal hone studies. The goal of this project is to clarify our understanding of the relationship between disorders of hearing and balance and PLY through correlative clinical-histopathologic investigations of human temporal bones. The results of the current project have produced supportive findings. (l) Defined clinical criteria to predict labyrinth capsule patencies (LCP): (a) Appear to have a high degree of accuracy [p< .001, sensitivity 59%, specificity 91%1 when tested using the histopathologic paradigm of this study, and (b) Applied in the clinical setting to the diagnosis of PLY reveal at surgery relationships between these patencies and sudden or rapidly progressive sensory hearing loss and specific types of vestibular disorders. (2) Fifty-seven patients-who have the diagnosis of PLY have bequeathed their temporal bones for histopathologic study and twenty-six others are in the process of completing their bequeathments. The temporal bones from one of these donors, who had vestibular symptoms relieved by surgery, have been procured and evaluated, histologically. These specimens demonstrate LCP by way of the fissula ante fenestram and the fissure of the round window niche posterior canal ampulla supporting the central hypothesis of the studies of this grant. (Ready for submission). (3) The collection of human temporal bone specimens from consecutive autopsies is providing strong preliminary statistical data regarding the frequency of occurrence of LCP and their association with cochlear and vestibular disorders. (4) The studies of apolipoproteins for purposes of developing a method for perilymph identification pre-operatively or at surgery indicate three types of these proteins with unique differences in concentration between perilymph, and serum or tissue fluid. (5) Animal studies indicate (a) the presence of naturally occurring LCP of the fossula post fenestram in squirrel monkeys (b)feasibility of bone conduction ABR in the cat, and (c) unreliable fluorescein concentration in perilymph in the cat. The proposed project will provide information to clarify the understanding of the pathogenesis and pathophysiology of PLF, the occurrence rate and histopathologic variations, further define the clinical criteria for accurate diagnosis and surgical methods using the consecutive autopsy/temporal bone studies, the predictive clinical/histopathologic temporal bone studies and the PLF patient temporal bone donor program. A reference regarding labyrinthine and brain cellular integrity (histologic) will be obtained through the perfused human temporal bones/brain study components of this project.